Imperial College London

DrPierreNouvellet

Faculty of MedicineSchool of Public Health

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Publications

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119 results found

Unwin H, Mishra S, Bradley V, Gandy A, Mellan T, Coupland H, Ish-Horowicz J, Vollmer M, Whittaker C, Filippi S, Xi X, Monod M, Ratmann O, Hutchinson M, Valka F, Zhu H, Hawryluk I, Milton P, Ainslie K, Baguelin M, Boonyasiri A, Brazeau N, Cattarino L, Cucunuba Z, Cuomo-Dannenburg G, Dorigatti I, Eales O, Eaton J, van Elsland S, Fitzjohn R, Gaythorpe K, Green W, Hinsley W, Jeffrey B, Knock E, Laydon D, Lees J, Nedjati-Gilani G, Nouvellet P, Okell L, Parag K, Siveroni I, Thompson H, Walker P, Walters C, Watson O, Whittles L, Ghani A, Ferguson N, Riley S, Donnelly C, Bhatt S, Flaxman Set al., 2020, State-level tracking of COVID-19 in the United States, Nature Communications, Vol: 11, Pages: 1-9, ISSN: 2041-1723

As of 1st June 2020, the US Centers for Disease Control and Prevention reported 104,232 confirmed or probable COVID-19-related deaths in the US. This was more than twice the number of deaths reported in the next most severely impacted country. We jointly model the US epidemic at the state-level, using publicly available deathdata within a Bayesian hierarchical semi-mechanistic framework. For each state, we estimate the number of individuals that have been infected, the number of individuals that are currently infectious and the time-varying reproduction number (the average number of secondary infections caused by an infected person). We use changes in mobility to capture the impact that non-pharmaceutical interventions and other behaviour changes have on therate of transmission of SARS-CoV-2. We estimate thatRtwas only below one in 23 states on 1st June. We also estimate that 3.7% [3.4%-4.0%] of the total population of the US had been infected, with wide variation between states, and approximately 0.01% of the population was infectious. We demonstrate good 3 week model forecasts of deaths with low error and good coverage of our credible intervals.

Journal article

Grassly NC, Pons-Salort M, Parker EPK, White PJ, Ferguson NM, Imperial College COVID-19 Response Teamet al., 2020, Comparison of molecular testing strategies for COVID-19 control: a mathematical modelling study, Lancet Infectious Diseases, Vol: 20, Pages: 1381-1389, ISSN: 1473-3099

BACKGROUND: WHO has called for increased testing in response to the COVID-19 pandemic, but countries have taken different approaches and the effectiveness of alternative strategies is unknown. We aimed to investigate the potential impact of different testing and isolation strategies on transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). METHODS: We developed a mathematical model of SARS-CoV-2 transmission based on infectiousness and PCR test sensitivity over time since infection. We estimated the reduction in the effective reproduction number (R) achieved by testing and isolating symptomatic individuals, regular screening of high-risk groups irrespective of symptoms, and quarantine of contacts of laboratory-confirmed cases identified through test-and-trace protocols. The expected effectiveness of different testing strategies was defined as the percentage reduction in R. We reviewed data on the performance of antibody tests reported by the Foundation for Innovative New Diagnostics and examined their implications for the use of so-called immunity passports. FINDINGS: If all individuals with symptoms compatible with COVID-19 self-isolated and self-isolation was 100% effective in reducing onwards transmission, self-isolation of symptomatic individuals would result in a reduction in R of 47% (95% uncertainty interval [UI] 32-55). PCR testing to identify SARS-CoV-2 infection soon after symptom onset could reduce the number of individuals needing to self-isolate, but would also reduce the effectiveness of self-isolation (around 10% would be false negatives). Weekly screening of health-care workers and other high-risk groups irrespective of symptoms by use of PCR testing is estimated to reduce their contribution to SARS-CoV-2 transmission by 23% (95% UI 16-40), on top of reductions achieved by self-isolation following symptoms, assuming results are available at 24 h. The effectiveness of test and trace depends strongly on coverage and the timelines

Journal article

Thompson H, Imai N, Dighe A, Ainslie K, Baguelin M, Bhatia S, Bhatt S, Boonyasiri A, Boyd O, Brazeau N, Cattarino L, Cooper L, Coupland H, Cucunuba Z, Cuomo-Dannenburg G, Djaafara B, Dorigatti I, van Elsland S, Fitzjohn R, Fu H, Gaythorpe K, Green W, Hallett T, Hamlet A, Haw D, Hayes S, Hinsley W, Jeffrey B, Knock E, Laydon D, Lees J, Mangal T, Mellan T, Mishra S, Mousa A, Nedjati-Gilani G, Nouvellet P, Okell L, Parag K, Ragonnet-Cronin M, Riley S, Unwin H, Verity R, Vollmer M, Volz E, Walker P, Walters C, Wang H, Wang Y, Watson O, Whittaker C, Whittles L, Winskill P, Xi X, Donnelly C, Ferguson Net al., 2020, SARS-CoV-2 infection prevalence on repatriation flights from Wuhan City, China, Journal of Travel Medicine, Vol: 27, Pages: 1-3, ISSN: 1195-1982

We estimated SARS-CoV-2 infection prevalence in cohorts of repatriated citizens from Wuhan to be 0.44% (95% CI: 0.19%–1.03%). Although not representative of the wider population we believe these estimates are helpful in providing a conservative estimate of infection prevalence in Wuhan City, China, in the absence of large-scale population testing early in the epidemic.

Journal article

Radhakrishnan S, Vanak AT, Nouvellet P, Donnelly Cet al., 2020, Rabies as a public health concern in India – a historical perspective, Tropical Medicine and Infectious Disease, Vol: 5, ISSN: 2414-6366

India bears the highest burden of global dog-mediated human rabies deaths. Despite this, rabies is not notifiable in India and continues to be underprioritised in public health discussions. This review examines the historical treatment of rabies in British India, a disease which has received relatively less attention in the literature on Indian medical history. Human and animal rabies was widespread in British India, and treatment of bite victims imposed a major financial burden on the colonial Government of India. It subsequently became a driver of Pasteurism in India and globally and a key component of British colonial scientific enterprise. Efforts to combat rabies led to the establishment of a wide network of research institutes in India and important breakthroughs in development of rabies vaccines. As a result of these efforts, rabies no longer posed a significant threat to the British, and it declined in administrative and public health priorities in India towards the end of colonial rule—a decline that has yet to be reversed in modern-day India. The review also highlights features of the administrative, scientific and societal approaches to dealing with this disease in British India that persist to this day.

Journal article

Dighe A, Cattarino L, Cuomo-Dannenburg G, Skarp J, Imai N, Bhatia S, Gaythorpe K, Ainslie K, Baguelin M, Bhatt S, Boonyasiri A, Brazeau N, Cooper L, Coupland H, Cucunuba Perez Z, Dorigatti I, Eales O, van Elsland S, Fitzjohn R, Green W, Haw D, Hinsley W, Knock E, Laydon D, Mellan T, Mishra S, Nedjati Gilani G, Nouvellet P, Pons Salort M, Thompson H, Unwin H, Verity R, Vollmer M, Walters C, Watson O, Whittaker C, Whittles L, Ghani A, Donnelly C, Ferguson N, Riley Set al., 2020, Response to COVID-19 in South Korea and implications for lifting stringent interventions, BMC Medicine, Vol: 18, Pages: 1-12, ISSN: 1741-7015

Background After experiencing a sharp growth in COVID-19 cases early in the pandemic, South Korea rapidly controlled transmission while implementing less stringent national social distancing measures than countries in Europe and the US. This has led to substantial interest in their “test, trace, isolate” strategy. However, it is important to understand the epidemiological peculiarities of South Korea’s outbreak and characterise their response before attempting to emulate these measures elsewhere.MethodsWe systematically extracted numbers of suspected cases tested, PCR-confirmed cases, deaths, isolated confirmed cases, and numbers of confirmed cases with an identified epidemiological link from publicly available data. We estimated the time-varying reproduction number, Rt, using an established Bayesian framework, and reviewed the package of interventions implemented by South Korea using our extracted data, plus published literature and government sources. Results We estimated that after the initial rapid growth in cases, Rt dropped below one in early April before increasing to a maximum of 1.94 (95%CrI; 1.64-2.27) in May following outbreaks in Seoul Metropolitan Region. By mid-June Rt was back below one where it remained until the end of our study (July 13th). Despite less stringent “lockdown” measures, strong social distancing measures were implemented in high incidence areas and studies measured a considerable national decrease in movement in late-February. Testing capacity was swiftly increased, and protocols were in place to isolate suspected and confirmed cases quickly however we could not estimate the delay to isolation using our data. Accounting for just 10% of cases, individual case-based contact-tracing picked up a relatively minor proportion of total cases, with cluster investigations accounting for 66%. ConclusionsWhilst early adoption of testing and contact-tracing are likely to be important for South Korea’s successf

Journal article

Djaafara BA, Whittaker C, Watson OJ, Verity R, Brazeau NF, Widyastuti W, Oktavia D, Adrian V, Salama N, Bhatia S, Nouvellet P, Sherrard-Smith E, Churcher TS, Surendra H, Lina RN, Ekawati LL, Lestari KD, Andrianto A, Thwaites G, Baird JK, Ghani AC, Elyazar IRF, Walker PGTet al., 2020, Quantifying the dynamics of COVID-19 burden and impact of interventions in Java, Indonesia

<jats:title>ABSTRACT</jats:title><jats:sec><jats:title>Background</jats:title><jats:p>As in many countries, quantifying COVID-19 spread in Indonesia remains challenging due to testing limitations. In Java, non-pharmaceutical interventions (NPIs) were implemented throughout 2020. However, as a vaccination campaign launches, cases and deaths are rising across the island.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>We used modelling to explore the extent to which data on burials in Jakarta using strict COVID-19 protocols (C19P) provide additional insight into the transmissibility of the disease, epidemic trajectory, and the impact of NPIs. We assess how implementation of NPIs in early 2021 will shape the epidemic during the period of likely vaccine roll-out.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>C19P burial data in Jakarta suggest a death toll approximately 3.3 times higher than reported. Transmission estimates using these data suggest earlier, larger, and more sustained impact of NPIs. Measures to reduce sub-national spread, particularly during Ramadan, substantially mitigated spread to more vulnerable rural areas. Given current trajectory, daily cases and deaths are likely to increase in most regions as the vaccine is rolled-out. Transmission may peak in early 2021 in Jakarta if current levels of control are maintained. However, relaxation of control measures is likely to lead to a subsequent resurgence in the absence of an effective vaccination campaign.</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>Syndromic measures of mortality provide a more complete picture of COVID-19 severity upon which to base decision-making. The high potential impact of the vaccine in Java is attributable to reductions in transmission to date and dependent on these be

Journal article

Hogan A, Winskill P, Watson O, Walker P, Whittaker C, Baguelin M, Haw D, Lochen A, Gaythorpe K, Ainslie K, Bhatt S, Boonyasiri A, Boyd O, Brazeau N, Cattarino L, Charles G, Cooper L, Coupland H, Cucunuba Perez Z, Cuomo-Dannenburg G, Donnelly C, Dorigatti I, Eales O, van Elsland S, Ferreira Do Nascimento F, Fitzjohn R, Flaxman S, Green W, Hallett T, Hamlet A, Hinsley W, Imai N, Jauneikaite E, Jeffrey B, Knock E, Laydon D, Lees J, Mellan T, Mishra S, Nedjati Gilani G, Nouvellet P, Ower A, Parag K, Ragonnet-Cronin M, Siveroni I, Skarp J, Thompson H, Unwin H, Verity R, Vollmer M, Volz E, Walters C, Wang H, Wang Y, Whittles L, Xi X, Muhib F, Smith P, Hauck K, Ferguson N, Ghani Aet al., 2020, Report 33: Modelling the allocation and impact of a COVID-19 vaccine

Several SARS-CoV-2 vaccine candidates are now in late-stage trials, with efficacy and safety results expected by the end of 2020. Even under optimistic scenarios for manufacture and delivery, the doses available in 2021 are likely to be limited. Here we identify optimal vaccine allocation strategies within and between countries to maximise health (avert deaths) under constraints on dose supply. We extended an existing mathematical model of SARS-CoV-2 transmission across different country settings to model the public health impact of potential vaccines, using a range of target product profiles developed by the World Health Organization. We show that as supply increases, vaccines that reduce or block infection – and thus transmission – in addition to preventing disease have a greater impact than those that prevent disease alone, due to the indirect protection provided to high-risk groups. We further demonstrate that the health impact of vaccination will depend on the cumulative infection incidence in the population when vaccination begins, the duration of any naturally acquired immunity, the likely trajectory of the epidemic in 2021 and the level of healthcare available to effectively treat those with disease. Within a country, we find that for a limited supply (doses for <20% of the population) the optimal strategy is to target the elderly and other high-risk groups. However, if a larger supply is available, the optimal strategy switches to targeting key transmitters (i.e. the working age population and potentially children) to indirectly protect the elderly and vulnerable. Given the likely global dose supply in 2021 (2 billion doses with a two-dose vaccine), we find that a strategy in which doses are allocated to countries in proportion to their population size is close to optimal in averting deaths. Such a strategy also aligns with the ethical principles agreed in pandemic preparedness planning.

Report

Radhakrishnan S, Vanak AT, Nouvellet P, Donnelly CAet al., 2020, Rabies as a Public Health Concern in India – A Historical Perspective

<jats:p>India bears the highest burden of global dog-mediated human rabies deaths. Despite this, rabies is not notifiable in India, and continues to be underprioritized in public health discussions. This review examines the historical treatment of rabies in British India, a disease which has received relatively less attention in the literature on Indian medical history. Human and animal rabies was widespread in British India and treatment of bite victims imposed a major financial burden on the colonial Government of India. It subsequently became a driver of Pasteurism in India and globally and a key component of British colonial scientific enterprise. Efforts to combat rabies led to the establishment of a wide network of research institutes in India and important breakthroughs in development of rabies vaccines. As a result of these efforts, rabies no longer posed a significant threat to the British and it declined in administrative and public health priorities in India towards the end of colonial rule; a decline that has yet to be reversed in modern-day India. The review also highlights features of the administrative, scientific and societal approaches to dealing with this disease in British India which persist to this day.</jats:p>

Working paper

Monod M, Blenkinsop A, Xi X, Herbert D, Bershan S, Tietze S, Bradley V, Chen Y, Coupland H, Filippi S, Ish-Horowicz J, McManus M, Mellan T, Gandy A, Hutchinson M, Unwin H, Vollmer M, Weber S, Zhu H, Bezancon A, Ferguson N, Mishra S, Flaxman S, Bhatt S, Ratmann O, Ainslie K, Baguelin M, Boonyasiri A, Boyd O, Cattarino L, Cooper L, Cucunuba Perez Z, Cuomo-Dannenburg G, Djaafara A, Dorigatti I, van Elsland S, Fitzjohn R, Gaythorpe K, Geidelberg L, Green W, Hamlet A, Jeffrey B, Knock E, Laydon D, Nedjati Gilani G, Nouvellet P, Parag K, Siveroni I, Thompson H, Verity R, Walters C, Donnelly C, Okell L, Bhatia S, Brazeau N, Eales O, Haw D, Imai N, Jauneikaite E, Lees J, Mousa A, Olivera Mesa D, Skarp J, Whittles Let al., 2020, Report 32: Targeting interventions to age groups that sustain COVID-19 transmission in the United States, Pages: 1-32

Following ini􀀂al declines, in mid 2020, a resurgence in transmission of novel coronavirus disease (COVID-19) has occurred in the United States and parts of Europe. Despite the wide implementa􀀂on of non-pharmaceu􀀂cal inter-ven􀀂ons, it is s􀀂ll not known how they are impacted by changing contact pa􀀁erns, age and other demographics. As COVID-19 disease control becomes more localised, understanding the age demographics driving transmission and how these impact the loosening of interven􀀂ons such as school reopening is crucial. Considering dynamics for the United States, we analyse aggregated, age-specific mobility trends from more than 10 million individuals and link these mechanis􀀂cally to age-specific COVID-19 mortality data. In contrast to previous approaches, we link mobility to mortality via age specific contact pa􀀁erns and use this rich rela􀀂onship to reconstruct accurate trans-mission dynamics. Contrary to anecdotal evidence, we find li􀀁le support for age-shi􀀃s in contact and transmission dynamics over 􀀂me. We es􀀂mate that, un􀀂l August, 63.4% [60.9%-65.5%] of SARS-CoV-2 infec􀀂ons in the United States originated from adults aged 20-49, while 1.2% [0.8%-1.8%] originated from children aged 0-9. In areas with con􀀂nued, community-wide transmission, our transmission model predicts that re-opening kindergartens and el-ementary schools could facilitate spread and lead to considerable excess COVID-19 a􀀁ributable deaths over a 90-day period. These findings indicate that targe􀀂ng interven􀀂ons to adults aged 20-49 are an important con-sidera􀀂on in hal􀀂ng resurgent epidemics, and preven􀀂ng COVID-19-a􀀁ributable deaths when kindergartens and elementary schools reopen.

Journal article

van Elsland S, Watson O, Alhaffar M, Mehchy Z, Whittaker C, Akil Z, Ainslie K, Baguelin M, Bhatt S, Boonyasiri A, Boyd O, Brazeau N, Cattarino L, Charles G, Ciavarella C, Cooper L, Coupland H, Cucunuba Perez Z, Cuomo-Dannenburg G, Djaafara A, Donnelly C, Dorigatti I, Eales O, van Elsland S, Nascimento F, Fitzjohn R, Flaxman S, Forna A, Fu H, Gaythorpe K, Green W, Hamlet A, Hauck K, Haw D, Hayes S, Hinsley W, Imai N, Jeffrey B, Johnson R, Jorgensen D, Knock E, Laydon D, Lees J, Mellan T, Mishra S, Nedjati Gilani G, Nouvellet P, Okell L, Olivera Mesa D, Pons Salort M, Ragonnet-Cronin M, Siveroni I, Stopard I, Thompson H, Unwin H, Verity R, Vollmer M, Volz E, Walters C, Wang H, Wang Y, Whittles L, Winskill P, Xi X, Ferguson N, Beals E, Walker P, Anonymous Authorset al., 2020, Report 31: Estimating the burden of COVID-19 in Damascus, Syria: an analysis of novel data sources to infer mortality under-ascertainment

The COVID-19 pandemic has resulted in substantial mortality worldwide. However, to date, countries in the Middle East and Africa have reported substantially lower mortality rates than in Europe and the Americas. One hypothesis is that these countries have been ‘spared’, but another is that deaths have been under-ascertained (deaths that have been unreported due to any number of reasons, for instance due to limited testing capacity). However, the scale of under-ascertainment is difficult to assess with currently available data. In this analysis, we estimate the potential under-ascertainment of COVID-19 mortality in Damascus, Syria, where all-cause mortality data has been reported between 25th July and 1st August. We fit a mathematical model of COVID-19 transmission to reported COVID-19 deaths in Damascus since the beginning of the pandemic and compare the model-predicted deaths to reported excess deaths. Exploring a range of different assumptions about under-ascertainment, we estimate that only 1.25% of deaths (sensitivity range 1% - 3%) due to COVID-19 are reported in Damascus. Accounting for under-ascertainment also corroborates local reports of exceeded hospital bed capacity. To validate the epidemic dynamics inferred, we leverage community-uploaded obituary certificates as an alternative data source, which confirms extensive mortality under-ascertainment in Damascus between July and August. This level of under-ascertainment suggests that Damascus is at a much later stage in its epidemic than suggested by surveillance reports, which have repo. We estimate that 4,340 (95% CI: 3,250 - 5,540) deaths due to COVID-19 in Damascus may have been missed as of 2nd September 2020. Given that Damascus is likely to have the most robust surveillance in Syria, these findings suggest that other regions of the country could have experienced similar or worse mortality rates due to COVID-19.

Report

Charniga K, Cucunubá Z, Mercado M, Prieto F, Ospina M, Nouvellet P, Donnelly Cet al., 2020, Spatial and temporal invasion dynamics of the 2014-2017 Zika and chikungunya epidemics in Colombia, PLoS Computational Biology, ISSN: 1553-734X

Zika virus (ZIKV) and chikungunya virus (CHIKV) were recently introduced into the Americas resulting in significant disease burdens. Understanding their spatial and temporal dynamics at the subnational level is key to informing surveillance and preparedness for future epidemics. We analyzed anonymized line list data on approximately 105,000 Zika virus disease and 412,000 chikungunya fever suspected and laboratory-confirmed cases during the 2014-2017 epidemics. We first determined the week of invasion in each city. Out of 1,122, 288 cities met criteria for epidemic invasion by ZIKA and 338 cities by CHIKV. We estimated that the geographic origin of both epidemics was located in Barranquilla, north Colombia. Using gravity models, we assessed the spatial and temporal invasion dynamics of both viruses to analyze transmission between cities. Invasion risk was best captured when accounting for geographic distance and intermediate levels of density dependence. Although a few long-distance invasion events occurred at the beginning of the epidemics, an estimated distance power of 1.7 (95% CrI: 1.5-2.0) suggests that spatial spread was primarily driven by short-distance transmission. Cities with large populations were more likely to spread disease than cities with smaller populations. Similarities between the epidemics included having the same estimated geographic origin and having the same five parameters estimated in the best-fitting models. ZIKV spread considerably faster than CHIKV. <h4>Author summary</h4> Understanding the spread of infectious diseases across space and time is critical for preparedness, designing interventions, and elucidating mechanisms underlying transmission. We analyzed human case data from over 500,000 reported cases to investigate the spread of the recent Zika virus (ZIKV) and chikungunya virus (CHIKV) epidemics in Colombia. Both viruses were introduced into northern Colombia. We found that intermediate levels of density dependence best

Journal article

Hogan A, Jewell B, Sherrard-Smith E, Watson O, Whittaker C, Hamlet A, Smith J, Winskill P, Verity R, Baguelin M, Lees J, Whittles L, Ainslie K, Bhatt S, Boonyasiri A, Brazeau N, Cattarino L, Cooper L, Coupland H, Cuomo-Dannenburg G, Dighe A, Djaafara A, Donnelly C, Eaton J, van Elsland S, Fitzjohn R, Fu H, Gaythorpe K, Green W, Haw D, Hayes S, Hinsley W, Imai N, Laydon D, Mangal T, Mellan T, Mishra S, Parag K, Thompson H, Unwin H, Vollmer M, Walters C, Wang H, Ferguson N, Okell L, Churcher T, Arinaminpathy N, Ghani A, Walker P, Hallett Tet al., 2020, Potential impact of the COVID-19 pandemic on HIV, TB and malaria in low- and middle-income countries: a modelling study, The Lancet Global Health, Vol: 8, Pages: e1132-e1141, ISSN: 2214-109X

Background: COVID-19 has the potential to cause substantial disruptions to health services, including by cases overburdening the health system or response measures limiting usual programmatic activities. We aimed to quantify the extent to which disruptions in services for human immunodeficiency virus (HIV), tuberculosis (TB) and malaria in low- and middle-income countries with high burdens of those disease could lead to additional loss of life. Methods: We constructed plausible scenarios for the disruptions that could be incurred during the COVID-19 pandemic and used established transmission models for each disease to estimate the additional impact on health that could be caused in selected settings.Findings: In high burden settings, HIV-, TB- and malaria-related deaths over five years may increase by up to 10%, 20% and 36%, respectively, compared to if there were no COVID-19 pandemic. We estimate the greatest impact on HIV to be from interruption to antiretroviral therapy, which may occur during a period of high health system demand. For TB, we estimate the greatest impact is from reductions in timely diagnosis and treatment of new cases, which may result from any prolonged period of COVID-19 suppression interventions. We estimate that the greatest impact on malaria burden could come from interruption of planned net campaigns. These disruptions could lead to loss of life-years over five years that is of the same order of magnitude as the direct impact from COVID-19 in places with a high burden of malaria and large HIV/TB epidemics.Interpretation: Maintaining the most critical prevention activities and healthcare services for HIV, TB and malaria could significantly reduce the overall impact of the COVID-19 pandemic.Funding: Bill & Melinda Gates Foundation, The Wellcome Trust, DFID, MRC

Journal article

Lavezzo E, Franchin E, Ciavarella C, Cuomo-Dannenburg G, Barzon L, Del Vecchio C, Rossi L, Manganelli R, Loregian A, Navarin N, Abate D, Sciro M, Merigliano S, De Canale E, Vanuzzo MC, Besutti V, Saluzzo F, Onelia F, Pacenti M, Parisi S, Carretta G, Donato D, Flor L, Cocchio S, Masi G, Sperduti A, Cattarino L, Salvador R, Nicoletti M, Caldart F, Castelli G, Nieddu E, Labella B, Fava L, Drigo M, Gaythorpe KAM, Imperial College COVID-19 Response Team, Brazzale AR, Toppo S, Trevisan M, Baldo V, Donnelly CA, Ferguson NM, Dorigatti I, Crisanti Aet al., 2020, Suppression of a SARS-CoV-2 outbreak in the Italian municipality of Vo', Nature, Vol: 584, Pages: 425-429, ISSN: 0028-0836

On the 21st of February 2020 a resident of the municipality of Vo', a small town near Padua, died of pneumonia due to SARS-CoV-2 infection1. This was the first COVID-19 death detected in Italy since the emergence of SARS-CoV-2 in the Chinese city of Wuhan, Hubei province2. In response, the regional authorities imposed the lockdown of the whole municipality for 14 days3. We collected information on the demography, clinical presentation, hospitalization, contact network and presence of SARS-CoV-2 infection in nasopharyngeal swabs for 85.9% and 71.5% of the population of Vo' at two consecutive time points. On the first survey, which was conducted around the time the town lockdown started, we found a prevalence of infection of 2.6% (95% confidence interval (CI) 2.1-3.3%). On the second survey, which was conducted at the end of the lockdown, we found a prevalence of 1.2% (95% Confidence Interval (CI) 0.8-1.8%). Notably, 42.5% (95% CI 31.5-54.6%) of the confirmed SARS-CoV-2 infections detected across the two surveys were asymptomatic (i.e. did not have symptoms at the time of swab testing and did not develop symptoms afterwards). The mean serial interval was 7.2 days (95% CI 5.9-9.6). We found no statistically significant difference in the viral load of symptomatic versus asymptomatic infections (p-values 0.62 and 0.74 for E and RdRp genes, respectively, Exact Wilcoxon-Mann-Whitney test). This study sheds new light on the frequency of asymptomatic SARS-CoV-2 infection, their infectivity (as measured by the viral load) and provides new insights into its transmission dynamics and the efficacy of the implemented control measures.

Journal article

Flaxman S, Mishra S, Gandy A, Unwin HJT, Mellan TA, Coupland H, Whittaker C, Zhu H, Berah T, Eaton JW, Monod M, Perez Guzman PN, Schmit N, Cilloni L, Ainslie K, Baguelin M, Boonyasiri A, Boyd O, Cattarino L, Cucunuba Perez Z, Cuomo-Dannenburg G, Dighe A, Djaafara A, Dorigatti I, van Elsland S, Fitzjohn R, Gaythorpe K, Geidelberg L, Grassly N, Green W, Hallett T, Hamlet A, Hinsley W, Jeffrey B, Knock E, Laydon D, Nedjati Gilani G, Nouvellet P, Parag K, Siveroni I, Thompson H, Verity R, Volz E, Walters C, Wang H, Watson O, Winskill P, Xi X, Walker P, Ghani AC, Donnelly CA, Riley SM, Vollmer MAC, Ferguson NM, Okell LC, Bhatt Set al., 2020, Estimating the effects of non-pharmaceutical interventions on COVID-19 in Europe, Nature, Vol: 584, Pages: 257-261, ISSN: 0028-0836

Following the emergence of a novel coronavirus1 (SARS-CoV-2) and its spread outside of China, Europe has experienced large epidemics. In response, many European countries have implemented unprecedented non-pharmaceutical interventions such as closure of schools and national lockdowns. We study the impact of major interventions across 11 European countries for the period from the start of COVID-19 until the 4th of May 2020 when lockdowns started to be lifted. Our model calculates backwards from observed deaths to estimate transmission that occurred several weeks prior, allowing for the time lag between infection and death. We use partial pooling of information between countries with both individual and shared effects on the reproduction number. Pooling allows more information to be used, helps overcome data idiosyncrasies, and enables more timely estimates. Our model relies on fixed estimates of some epidemiological parameters such as the infection fatality rate, does not include importation or subnational variation and assumes that changes in the reproduction number are an immediate response to interventions rather than gradual changes in behavior. Amidst the ongoing pandemic, we rely on death data that is incomplete, with systematic biases in reporting, and subject to future consolidation. We estimate that, for all the countries we consider, current interventions have been sufficient to drive the reproduction number Rt below 1 (probability Rt< 1.0 is 99.9%) and achieve epidemic control. We estimate that, across all 11 countries, between 12 and 15 million individuals have been infected with SARS-CoV-2 up to 4th May, representing between 3.2% and 4.0% of the population. Our results show that major non-pharmaceutical interventions and lockdown in particular have had a large effect on reducing transmission. Continued intervention should be considered to keep transmission of SARS-CoV-2 under control.

Journal article

Fu H, Xi X, Wang H, Boonyasiri A, Wang Y, Hinsley W, Fraser K, McCabe R, Olivera Mesa D, Skarp J, Ledda A, Dewe T, Dighe A, Winskill P, van Elsland S, Ainslie K, Baguelin M, Bhatt S, Boyd O, Brazeau N, Cattarino L, Charles G, Coupland H, Cucunuba Perez Z, Cuomo-Dannenburg G, Donnelly C, Dorigatti I, Green W, Hamlet A, Hauck K, Haw D, Jeffrey B, Laydon D, Lees J, Mellan T, Mishra S, Nedjati Gilani G, Nouvellet P, Okell L, Parag K, Ragonnet-Cronin M, Riley S, Schmit N, Thompson H, Unwin H, Verity R, Vollmer M, Volz E, Walker P, Walters C, Watson O, Whittaker C, Whittles L, Imai N, Bhatia S, Ferguson Net al., 2020, Report 30: The COVID-19 epidemic trends and control measures in mainland China

Report

Forna A, Nouvellet P, Dorigatti I, Donnelly Cet al., 2020, Case fatality ratio estimates for the 2013 – 2016 West African Ebola epidemic: application of Boosted Regression Trees for imputation, Clinical Infectious Diseases, Vol: 70, Pages: 2476-2483, ISSN: 1058-4838

BackgroundThe 2013-2016 West African Ebola epidemic has been the largest to date with more than 11,000 deaths in the affected countries. The data collected have provided more insight than ever before into the case fatality ratio (CFR) and how it varies with age and other characteristics. However, the accuracy and precision of the naïve CFR remain limited because 44% of survival outcomes were unreported.MethodsUsing a Boosted Regression Tree (BRT) model, we imputed survival outcomes (i.e. survival or death) when unreported, corrected for model imperfection to estimate the CFR without imputation, with imputation and adjusted with imputation. The method allowed us to further identify and explore relevant clinical and demographic predictors of the CFR.ResultsThe out-of-sample performances of our model were good: sensitivity=69.7% (95% CI 52.5%-75.6%), specificity=69.8% (95% CI 54.1%-75.6%), percentage correctly classified=69.9% (95% CI 53.7%-75.5%) and area under the ROC curve= 76.0% (95% CI 56.8%-82.1%). The adjusted CFR estimates for the 2013-2016 West African epidemic were 82.8% (95% CI 45%.6-85.6%) overall and 89.1% (95% CI 40.8%-91.6%) , 65.6% (95% CI 61.3%-69.6%) and 79.2% (95% CI 45.4-84.1) for Sierra Leone, Guinea and Liberia, respectively. We found that district, hospitalisation status, age, case classification and quarter explained 93.6% of the variance in the naïve CFR.ConclusionsThe adjusted CFR estimates improved the naïve CFR estimates obtained without imputation and were more representative. Used in conjunction with other resources, adjusted estimates will inform public health contingency planning for future Ebola epidemic, and help better allocate resources and evaluate the effectiveness of future inventions.

Journal article

Nouvellet P, Bhatia S, Cori A, Ainslie K, Baguelin M, Bhatt S, Boonyasiri A, Brazeau N, Cattarino L, Cooper L, Coupland H, Cucunuba Perez Z, Cuomo-Dannenburg G, Dighe A, Djaafara A, Dorigatti I, Eales O, van Elsland S, Nscimento F, Fitzjohn R, Gaythorpe K, Geidelberg L, Grassly N, Green W, Hamlet A, Hauck K, Hinsley W, Imai N, Jeffrey B, Knock E, Laydon D, Lees J, Mangal T, Mellan T, Nedjati Gilani G, Parag K, Pons Salort M, Ragonnet-Cronin M, Riley S, Unwin H, Verity R, Vollmer M, Volz E, Walker P, Walters C, Wang H, Watson O, Whittaker C, Whittles L, Xi X, Ferguson N, Donnelly Cet al., 2020, Report 26: Reduction in mobility and COVID-19 transmission

In response to the COVID-19 pandemic, countries have sought to control transmission of SARS-CoV-2by restricting population movement through social distancing interventions, reducing the number ofcontacts.Mobility data represent an important proxy measure of social distancing. Here, we develop aframework to infer the relationship between mobility and the key measure of population-level diseasetransmission, the reproduction number (R). The framework is applied to 53 countries with sustainedSARS-CoV-2 transmission based on two distinct country-specific automated measures of humanmobility, Apple and Google mobility data.For both datasets, the relationship between mobility and transmission was consistent within andacross countries and explained more than 85% of the variance in the observed variation intransmissibility. We quantified country-specific mobility thresholds defined as the reduction inmobility necessary to expect a decline in new infections (R<1).While social contacts were sufficiently reduced in France, Spain and the United Kingdom to controlCOVID-19 as of the 10th of May, we find that enhanced control measures are still warranted for themajority of countries. We found encouraging early evidence of some decoupling of transmission andmobility in 10 countries, a key indicator of successful easing of social-distancing restrictions.Easing social-distancing restrictions should be considered very carefully, as small increases in contactrates are likely to risk resurgence even where COVID-19 is apparently under control. Overall, strongpopulation-wide social-distancing measures are effective to control COVID-19; however gradualeasing of restrictions must be accompanied by alternative interventions, such as efficient contacttracing, to ensure control.

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Jeffrey B, Walters C, Ainslie K, Eales O, Ciavarella C, Bhatia S, Hayes S, Baguelin M, Boonyasiri A, Brazeau N, Cuomo-Dannenburg G, Fitzjohn R, Gaythorpe K, Green W, Imai N, Mellan T, Mishra S, Nouvellet P, Unwin H, Verity R, Vollmer M, Whittaker C, Ferguson N, Donnelly C, Riley Set al., 2020, Report 24: Mobility data from mobile phones suggests that initial compliance with COVID-19 social distancing interventions was high and geographically consistent across the UK, 24

Since early March 2020, the COVID-19 epidemic across the United Kingdom has led to a range of socialdistancing policies, which have resulted in reduced mobility across different regions. Crowd level dataon mobile phone usage can be used as a proxy for actual population mobility patterns and provide away of quantifying the impact of social distancing measures on changes in mobility. Here, we use twomobile phone-based datasets (anonymised and aggregated crowd level data from O2 and from theFacebook app on mobile phones) to assess changes in average mobility, both overall and broken downinto high and low population density areas, and changes in the distribution of journey lengths. Weshow that there was a substantial overall reduction in mobility with the most rapid decline on the 24thMarch 2020, the day after the Prime Minister’s announcement of an enforced lockdown. Thereduction in mobility was highly synchronized across the UK. Although mobility has remained low since26th March 2020, we detect a gradual increase since that time. We also show that the two differentdatasets produce similar trends, albeit with some location-specific differences. We see slightly largerreductions in average mobility in high-density areas than in low-density areas, with greater variationin mobility in the high-density areas: some high-density areas eliminated almost all mobility. We areonly able to observe populations living in locations where sufficient number of people use Facebookor a device connected to the relevant provider’s network such that no individual is identifiable. Theseanalyses form a baseline with which to monitor changes in behaviour in the UK as social distancing iseased.

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Dighe A, Cattarino L, Cuomo-Dannenburg G, Skarp J, Imai N, Bhatia S, Gaythorpe K, Ainslie K, Baguelin M, Bhatt S, Boonyasiri A, Boyd O, Brazeau N, Charles G, Cooper L, Coupland H, Cucunuba Perez Z, Djaafara A, Dorigatti I, Eales O, Eaton J, van Elsland S, Ferreira Do Nascimento F, Fitzjohn R, Flaxman S, Fraser K, Geidelberg L, Green W, Hallett T, Hamlet A, Hauck K, Haw D, Hinsley W, Jeffrey B, Knock E, Laydon D, Lees J, Mellan T, Mishra S, Nedjati Gilani G, Nouvellet P, Okell L, Parag K, Pons Salort M, Ragonnet-Cronin M, Thompson H, Unwin H, Verity R, Whittaker C, Whittles L, Xi X, Ghani A, Donnelly C, Ferguson N, Riley Set al., 2020, Report 25: Response to COVID-19 in South Korea and implications for lifting stringent interventions, 25

While South Korea experienced a sharp growth in COVID-19 cases early in the global pandemic, it has since rapidly reduced rates of infection and now maintains low numbers of daily new cases. Despite using less stringent “lockdown” measures than other affected countries, strong social distancing measures have been advised in high incidence areas and a 38% national decrease in movement occurred voluntarily between February 24th - March 1st. Suspected and confirmed cases were isolated quickly even during the rapid expansion of the epidemic and identification of the Shincheonji cluster. South Korea swiftly scaled up testing capacity and was able to maintain case-based interventions throughout. However, individual case-based contact tracing, not associated with a specific cluster, was a relatively minor aspect of their control program, with cluster investigations accounting for a far higher proportion of cases: the underlying epidemic was driven by a series of linked clusters, with 48% of all cases in the Shincheonji cluster and 20% in other clusters. Case-based contacts currently account for only 11% of total cases. The high volume of testing and low number of deaths suggests that South Korea experienced a small epidemic of infections relative to other countries. Therefore, caution is needed in attempting to duplicate the South Korean response in settings with larger more generalized epidemics. Finding, testing and isolating cases that are linked to clusters may be more difficult in such settings.

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Mellan TA, Hoeltgebaum HH, Mishra S, Whittaker C, Schnekenberg RP, Gandy A, Unwin HJT, Vollmer MAC, Coupland H, Hawryluk I, Faria NR, Vesga J, Zhu H, Hutchinson M, Ratmann O, Monod M, Ainslie KEC, Baguelin M, Bhatia S, Boonyasiri A, Brazeau N, Charles G, Cucunuba Z, Cuomo-Dannenburg G, Dighe A, Eaton J, Elsland SLV, Gaythorpe KAM, Green W, Knock E, Laydon D, Lees JA, Mousa A, Nedjati-Gilani G, Nouvellet P, Parag KV, Thompson HA, Verity R, Walters CE, Wang H, Wang Y, Watson OJ, Whittles L, Xi X, Dorigatti I, Walker P, Ghani AC, Riley S, Ferguson NM, Donnelly CA, Flaxman S, Bhatt Set al., 2020, Subnational analysis of the COVID-19 epidemic in Brazil

<jats:label>1</jats:label><jats:title>Abstract</jats:title><jats:p>Brazil is currently reporting the second highest number of COVID-19 deaths in the world. Here we characterise the initial dynamics of COVID-19 across the country and assess the impact of non-pharmaceutical interventions (NPIs) that were implemented using a semi-mechanistic Bayesian hierarchical modelling approach. Our results highlight the significant impact these NPIs had across states, reducing an average <jats:italic>R<jats:sub>t</jats:sub> &gt;</jats:italic> 3 to an average of 1.5 by 9-May-2020, but that these interventions failed to reduce <jats:italic>R<jats:sub>t</jats:sub></jats:italic> &lt; 1, congruent with the worsening epidemic Brazil has experienced since. We identify extensive heterogeneity in the epidemic trajectory across Brazil, with the estimated number of days to reach 0.1% of the state population infected since the first nationally recorded case ranging from 20 days in São Paulo compared to 60 days in Goiás, underscoring the importance of sub-national analyses in understanding asynchronous state-level epidemics underlying the national spread and burden of COVID-19.</jats:p>

Journal article

Winskill P, Whittaker C, Walker P, Watson O, Laydon D, Imai N, Cuomo-Dannenburg G, Ainslie K, Baguelin M, Bhatt S, Boonyasiri A, Cattarino L, Ciavarella C, Cooper L, Coupland H, Cucunuba Perez Z, van Elsland S, Fitzjohn R, Flaxman S, Gaythorpe K, Green W, Hallett T, Hamlet A, Hinsley W, Knock E, Lees J, Mellan T, Mishra S, Nedjati Gilani G, Nouvellet P, Okell L, Parag K, Thompson H, Unwin H, Wang Y, Whittles L, Xi X, Ferguson N, Donnelly C, Ghani Aet al., 2020, Report 22: Equity in response to the COVID-19 pandemic: an assessment of the direct and indirect impacts on disadvantaged and vulnerable populations in low- and lower middle-income countries, 22

The impact of the COVID-19 pandemic in low-income settings is likely to be more severe due to limited healthcare capacity. Within these settings, however, there exists unfair or avoidable differences in health among different groups in society – health inequities – that mean that some groups are particularly at risk from the negative direct and indirect consequences of COVID-19. The structural determinants of these are often reflected in differences by income strata, with the poorest populations having limited access to preventative measures such as handwashing. Their more fragile income status will also mean that they are likely to be employed in occupations that are not amenable to social-distancing measures, thereby further reducing their ability to protect themselves from infection. Furthermore, these populations may also lack access to timely healthcare on becoming ill. We explore these relationships by using large-scale household surveys to quantify the differences in handwashing access, occupation and hospital access with respect to wealth status in low-income settings. We use a COVID-19 transmission model to demonstrate the impact of these differences. Our results demonstrate clear trends that the probability of death from COVID-19 increases with increasing poverty. On average, we estimate a 32.0% (2.5th-97.5th centile 8.0%-72.5%) increase in the probability of death in the poorest quintile compared to the wealthiest quintile from these three factors alone. We further explore how risk mediators and the indirect impacts of COVID-19 may also hit these same disadvantaged and vulnerable the hardest. We find that larger, inter-generational households that may hamper efforts to protect the elderly if social distancing are associated with lower-income countries and, within LMICs, lower wealth status. Poorer populations are also more susceptible to food security issues - with these populations having the highest levels under-nourishment whilst also being

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Vollmer M, Mishra S, Unwin J, Gandy A, Mellan T, Bradley V, Zhu H, Coupland H, Hawryluk I, Hutchinson M, Ratmann O, Monod M, Walker P, Whittaker C, Cattarino L, Ciavarella C, Cilloni L, Ainslie K, Baguelin M, Bhatia S, Boonyasiri A, Brazeau N, Charles G, Cooper L, Cucunuba Z, Cuomo-Dannenburg G, Dighe A, Djaafara B, Eaton J, van Elsland S, FitzJohn R, Fraser K, Gaythorpe K, Green W, Hayes S, Imai N, Jeffrey B, Knock E, Laydon D, Lees J, Mangal T, Mousa A, Nedjati-Gilani G, Nouvellet P, Olivera D, Parag K, Pickles M, Thompson H, Verity R, Walters C, Wang H, Wang Y, Watson O, Whittles L, Xi X, Ghani A, Riley S, Okell L, Donnelly C, Ferguson N, Dorigatti I, Flaxman S, Bhatt Set al., 2020, A sub-national analysis of the rate of transmission of COVID-19 in Italy, medRxiv

Italy was the first European country to experience sustained local transmission of COVID-19. As of 1st May 2020, the Italian health authorities reported 28,238 deaths nationally. To control the epidemic, the Italian government implemented a suite of non-pharmaceutical interventions (NPIs), including school and university closures, social distancing and full lockdown involving banning of public gatherings and non essential movement. In this report, we model the effect of NPIs on transmission using data on average mobility. We estimate that the average reproduction number (a measure of transmission intensity) is currently below one for all Italian regions, and significantly so for the majority of the regions. Despite the large number of deaths, the proportion of population that has been infected by SARS-CoV-2 (the attack rate) is far from the herd immunity threshold in all Italian regions, with the highest attack rate observed in Lombardy (13.18% [10.66%-16.70%]). Italy is set to relax the currently implemented NPIs from 4th May 2020. Given the control achieved by NPIs, we consider three scenarios for the next 8 weeks: a scenario in which mobility remains the same as during the lockdown, a scenario in which mobility returns to pre-lockdown levels by 20%, and a scenario in which mobility returns to pre-lockdown levels by 40%. The scenarios explored assume that mobility is scaled evenly across all dimensions, that behaviour stays the same as before NPIs were implemented, that no pharmaceutical interventions are introduced, and it does not include transmission reduction from contact tracing, testing and the isolation of confirmed or suspected cases. New interventions, such as enhanced testing and contact tracing are going to be introduced and will likely contribute to reductions in transmission; therefore our estimates should be viewed as pessimistic projections. We find that, in the absence of additional interventions, even a 20% return to pre-lockdown mobility could le

Journal article

Mellan T, Hoeltgebaum H, Mishra S, Whittaker C, Schnekenberg R, Gandy A, Unwin H, Vollmer M, Coupland H, Hawryluk I, Rodrigues Faria N, Vesga J, Zhu H, Hutchinson M, Ratmann O, Monod M, Ainslie K, Baguelin M, Bhatia S, Boonyasiri A, Brazeau N, Charles G, Cooper L, Cucunuba Perez Z, Cuomo-Dannenburg G, Dighe A, Djaafara A, Eaton J, van Elsland S, Fitzjohn R, Fraser K, Gaythorpe K, Green W, Hayes S, Imai N, Jeffrey B, Knock E, Laydon D, Lees J, Mangal T, Mousa A, Nedjati Gilani G, Nouvellet P, Olivera Mesa D, Parag K, Pickles M, Thompson H, Verity R, Walters C, Wang H, Wang Y, Watson O, Whittles L, Xi X, Okell L, Dorigatti I, Walker P, Ghani A, Riley S, Ferguson N, Donnelly C, Flaxman S, Bhatt Set al., 2020, Report 21: Estimating COVID-19 cases and reproduction number in Brazil

Brazil is an epicentre for COVID-19 in Latin America. In this report we describe the Brazilian epidemicusing three epidemiological measures: the number of infections, the number of deaths and the reproduction number. Our modelling framework requires sufficient death data to estimate trends, and wetherefore limit our analysis to 16 states that have experienced a total of more than fifty deaths. Thedistribution of deaths among states is highly heterogeneous, with 5 states—São Paulo, Rio de Janeiro,Ceará, Pernambuco and Amazonas—accounting for 81% of deaths reported to date. In these states, weestimate that the percentage of people that have been infected with SARS-CoV-2 ranges from 3.3% (95%CI: 2.8%-3.7%) in São Paulo to 10.6% (95% CI: 8.8%-12.1%) in Amazonas. The reproduction number (ameasure of transmission intensity) at the start of the epidemic meant that an infected individual wouldinfect three or four others on average. Following non-pharmaceutical interventions such as school closures and decreases in population mobility, we show that the reproduction number has dropped substantially in each state. However, for all 16 states we study, we estimate with high confidence that thereproduction number remains above 1. A reproduction number above 1 means that the epidemic isnot yet controlled and will continue to grow. These trends are in stark contrast to other major COVID19 epidemics in Europe and Asia where enforced lockdowns have successfully driven the reproductionnumber below 1. While the Brazilian epidemic is still relatively nascent on a national scale, our resultssuggest that further action is needed to limit spread and prevent health system overload.

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Vollmer M, Mishra S, Unwin H, Gandy A, Melan T, Bradley V, Zhu H, Coupland H, Hawryluk I, Hutchinson M, Ratmann O, Monod M, Walker P, Whittaker C, Cattarino L, Ciavarella C, Cilloni L, Ainslie K, Baguelin M, Bhatia S, Boonyasiri A, Brazeau N, Charles G, Cooper L, Cucunuba Perez Z, Cuomo-Dannenburg G, Dighe A, Djaafara A, Eaton J, van Elsland S, Fitzjohn R, Gaythorpe K, Green W, Hayes S, Imai N, Jeffrey B, Knock E, Laydon D, Lees J, Mangal T, Mousa A, Nedjati Gilani G, Nouvellet P, Olivera Mesa D, Parag K, Pickles M, Thompson H, Verity R, Walters C, Wang H, Wang Y, Watson O, Whittles L, Xi X, Ghani A, Riley S, Okell L, Donnelly C, Ferguson N, Dorigatti I, Flaxman S, Bhatt Set al., 2020, Report 20: A sub-national analysis of the rate of transmission of Covid-19 in Italy

Italy was the first European country to experience sustained local transmission of COVID-19. As of 1st May 2020, the Italian health authorities reported 28; 238 deaths nationally. To control the epidemic, the Italian government implemented a suite of non-pharmaceutical interventions (NPIs), including school and university closures, social distancing and full lockdown involving banning of public gatherings and non essential movement. In this report, we model the effect of NPIs on transmission using data on average mobility. We estimate that the average reproduction number (a measure of transmission intensity) is currently below one for all Italian regions, and significantly so for the majority of the regions. Despite the large number of deaths, the proportion of population that has been infected by SARS-CoV-2 (the attack rate) is far from the herd immunity threshold in all Italian regions, with the highest attack rate observed in Lombardy (13.18% [10.66%-16.70%]). Italy is set to relax the currently implemented NPIs from 4th May 2020. Given the control achieved by NPIs, we consider three scenarios for the next 8 weeks: a scenario in which mobility remains the same as during the lockdown, a scenario in which mobility returns to pre-lockdown levels by 20%, and a scenario in which mobility returns to pre-lockdown levels by 40%. The scenarios explored assume that mobility is scaled evenly across all dimensions, that behaviour stays the same as before NPIs were implemented, that no pharmaceutical interventions are introduced, and it does not include transmission reduction from contact tracing, testing and the isolation of confirmed or suspected cases. We find that, in the absence of additional interventions, even a 20% return to pre-lockdown mobility could lead to a resurgence in the number of deaths far greater than experienced in the current wave in several regions. Future increases in the number of deaths will lag behind the increase in transmission intensity and so a

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Li C, Zhang Y, Nouvellet P, Okoro JO, Xiao W, Harder MKet al., 2020, Distance is a barrier to recycling - or is it? Surprises from a clean test, WASTE MANAGEMENT, Vol: 108, Pages: 183-188, ISSN: 0956-053X

Journal article

Grassly N, Pons Salort M, Parker E, White P, Ainslie K, Baguelin M, Bhatt S, Boonyasiri A, Boyd O, Brazeau N, Cattarino L, Ciavarella C, Cooper L, Coupland H, Cucunuba Perez Z, Cuomo-Dannenburg G, Dighe A, Djaafara A, Donnelly C, Dorigatti I, van Elsland S, Ferreira Do Nascimento F, Fitzjohn R, Fu H, Gaythorpe K, Geidelberg L, Green W, Hallett T, Hamlet A, Hayes S, Hinsley W, Imai N, Jorgensen D, Knock E, Laydon D, Lees J, Mangal T, Mellan T, Mishra S, Nedjati Gilani G, Nouvellet P, Okell L, Ower A, Parag K, Pickles M, Ragonnet-Cronin M, Stopard I, Thompson H, Unwin H, Verity R, Vollmer M, Volz E, Walker P, Walters C, Wang H, Wang Y, Watson O, Whittaker C, Whittles L, Winskill P, Xi X, Ferguson Net al., 2020, Report 16: Role of testing in COVID-19 control

The World Health Organization has called for increased molecular testing in response to the COVID-19 pandemic, but different countries have taken very different approaches. We used a simple mathematical model to investigate the potential effectiveness of alternative testing strategies for COVID-19 control. Weekly screening of healthcare workers (HCWs) and other at-risk groups using PCR or point-of-care tests for infection irrespective of symptoms is estimated to reduce their contribution to transmission by 25-33%, on top of reductions achieved by self-isolation following symptoms. Widespread PCR testing in the general population is unlikely to limit transmission more than contact-tracing and quarantine based on symptoms alone, but could allow earlier release of contacts from quarantine. Immunity passports based on tests for antibody or infection could support return to work but face significant technical, legal and ethical challenges. Testing is essential for pandemic surveillance but its direct contribution to the prevention of transmission is likely to be limited to patients, HCWs and other high-risk groups.

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Forna A, Dorigatti I, Nouvellet P, Donnelly Cet al., 2020, Spatiotemporal variability in case fatality ratios for 2013–2016 Ebola epidemic in West Africa, International Journal of Infectious Diseases, Vol: 93, Pages: 48-55, ISSN: 1201-9712

Background: For the 2013–2016 Ebola epidemic in West Africa, the largest Ebola virus disease (EVD)epidemic to date, we aim to analyse the patient mix in detail to characterise key sources ofspatiotemporal heterogeneity in the case fatality ratios (CFR).Methods: We applied a non-parametric Boosted Regression Trees (BRT) imputation approach for patientswith missing survival outcomes and adjusted for model imperfection. Semivariogram analysis andkriging were used to investigate spatiotemporal heterogeneities.Results: CFR estimates varied significantly between districts and over time over the course of theepidemic. BRT modelling accounted for most of the spatiotemporal variation and interactions in CFR, butmoderate spatial autocorrelation remained for distances up to approximately 90 km. Combining districtlevel CFR estimates and kriged district-level residuals provided the best linear unbiased predicted map ofCFR accounting for the both explained and unexplained spatial variation. Temporal autocorrelation wasnot observed in the district-level residuals from the BRT estimates.Conclusions: This study provides new insight into the epidemiology of the 2013–2016 West African Ebolaepidemic with a view of informing future public health contingency planning, resource allocation andimpact assessment. The analytical framework developed in this analysis, coupled with key domainknowledge, could be deployed in real time to support the response to ongoing and future outbreaks.

Journal article

Gold S, Donnelly C, Nouvellet P, Woodroffe Ret al., 2020, Rabies virus neutralising antibodies in healthy, unvaccinated individuals: What do they mean for rabies epidemiology?, PLoS Neglected Tropical Diseases, ISSN: 1935-2727

Rabies has been a widely feared disease for thousands of years, with records of rabid dogs as early as ancient Egyptian and Mesopotamian texts. The reputation of rabies as being inevitably fatal, together with its ability to affect all mammalian species, contributes to the fear surrounding this disease. However, the widely held view that exposure to the rabies virus is always fatal has been repeatedly challenged. Although survival following clinical infection in humans has only been recorded on a handful of occasions, a number of studies have reported detection of rabies-specific antibodies in the sera of humans, domestic animals and wildlife which are apparently healthy and unvaccinated. These “seropositive” individuals provide possible evidence of exposure to the rabies virus which has not led to fatal disease. However, the variability in methods of detecting these antibodies and the difficulties of interpreting serology tests have contributed to an unclear picture of their importance. In this review we consider the evidence for rabies-specific antibodies in healthy, unvaccinated individuals as indicators of non-lethal rabies exposure and the potential implications of this for rabies epidemiology. Our findings indicate that while there is substantial evidence that non-lethal rabies exposure does occur, serology studies which do not use appropriate controls and cut-offs are unlikely to provide an accurate estimate of the true prevalence of non-lethal rabies exposure.

Journal article

Jeffrey B, Walters CE, Ainslie KEC, Eales O, Ciavarella C, Bhatia S, Hayes S, Baguelin M, Boonyasiri A, Brazeau NF, Cuomo-Dannenburg G, FitzJohn RG, Gaythorpe K, Green W, Imai N, Mellan TA, Mishra S, Nouvellet P, Unwin HJT, Verity R, Vollmer M, Whittaker C, Ferguson NM, Donnelly CA, Riley Set al., 2020, Anonymised and aggregated crowd level mobility data from mobile phones suggests that initial compliance with COVID-19 social distancing interventions was high and geographically consistent across the UK., Wellcome open research, Vol: 5, ISSN: 2398-502X

<b>Background:</b> Since early March 2020, the COVID-19 epidemic across the United Kingdom has led to a range of social distancing policies, which have resulted in reduced mobility across different regions. Crowd level data on mobile phone usage can be used as a proxy for actual population mobility patterns and provide a way of quantifying the impact of social distancing measures on changes in mobility. <b>Methods:</b> Here, we use two mobile phone-based datasets (anonymised and aggregated crowd level data from O2 and from the Facebook app on mobile phones) to assess changes in average mobility, both overall and broken down into high and low population density areas, and changes in the distribution of journey lengths. <b>Results:</b> We show that there was a substantial overall reduction in mobility, with the most rapid decline on the 24th March 2020, the day after the Prime Minister's announcement of an enforced lockdown. The reduction in mobility was highly synchronized across the UK. Although mobility has remained low since 26th March 2020, we detect a gradual increase since that time. We also show that the two different datasets produce similar trends, albeit with some location-specific differences. We see slightly larger reductions in average mobility in high-density areas than in low-density areas, with greater variation in mobility in the high-density areas: some high-density areas eliminated almost all mobility. <b>Conclusions:</b> These analyses form a baseline from which to observe changes in behaviour in the UK as social distancing is eased and inform policy towards the future control of SARS-CoV-2 in the UK.

Journal article

Jeffrey B, Walters CE, Ainslie KEC, Eales O, Ciavarella C, Bhatia S, Hayes S, Baguelin M, Boonyasiri A, Brazeau NF, Cuomo-Dannenburg G, FitzJohn RG, Gaythorpe K, Green W, Imai N, Mellan TA, Mishra S, Nouvellet P, Unwin HJT, Verity R, Vollmer M, Whittaker C, Ferguson NM, Donnelly CA, Riley Set al., 2020, Anonymised and aggregated crowd level mobility data from mobile phones suggests that initial compliance with COVID-19 social distancing interventions was high and geographically consistent across the UK., Wellcome Open Res, Vol: 5, ISSN: 2398-502X

Background: Since early March 2020, the COVID-19 epidemic across the United Kingdom has led to a range of social distancing policies, which have resulted in reduced mobility across different regions. Crowd level data on mobile phone usage can be used as a proxy for actual population mobility patterns and provide a way of quantifying the impact of social distancing measures on changes in mobility. Methods: Here, we use two mobile phone-based datasets (anonymised and aggregated crowd level data from O2 and from the Facebook app on mobile phones) to assess changes in average mobility, both overall and broken down into high and low population density areas, and changes in the distribution of journey lengths. Results: We show that there was a substantial overall reduction in mobility, with the most rapid decline on the 24th March 2020, the day after the Prime Minister's announcement of an enforced lockdown. The reduction in mobility was highly synchronized across the UK. Although mobility has remained low since 26th March 2020, we detect a gradual increase since that time. We also show that the two different datasets produce similar trends, albeit with some location-specific differences. We see slightly larger reductions in average mobility in high-density areas than in low-density areas, with greater variation in mobility in the high-density areas: some high-density areas eliminated almost all mobility. Conclusions: These analyses form a baseline from which to observe changes in behaviour in the UK as social distancing is eased and inform policy towards the future control of SARS-CoV-2 in the UK.

Journal article

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